ABSTRACT This proposal describes the development of the HydrAid Burn Dressing?a novel hydrogel-based burn wound dressing that absorbs exudate, protects the wound from bacterial infection and can be easily removed from the wound surface of a 2nd degree burn without causing trauma to the wound or pain to the patient. Burns are one of the most common and devastating forms of trauma. Each year, more than 300,000 people worldwide die from fire-related burn injuries and millions more suffer from burn-related disabilities and disfigurements with psychological, social, and economic effects on both the survivors and their families. Burn dressing removal is reported to be the time of most pain (after the burn itself) and opioids continue to be the mainstay of treatment for burn patients. The duration of a burn dressing change in a typical injury requiring ICU/OR level care is often at least 60 minutes with induction of general anesthesia, and can extend to more than three hours depending on the case. At present, all clinically available dressings adhere to the wound surface so that each change of dressing leads to traumatization of newly formed tissues on the outer layer of the body's surface, delayed healing and excruciating pain for the injured patient. The HydrAid Burn Dressing is composed of an amine-terminated dendron and a bifunctional NHS-activated PEG containing an internal thioester that react with each other to form a thioester-linked hydrogel dressing that can be subsequently dissolved by exposure to an aqueous thiol solution via a thiol-thioester exchange mechanism. Preliminary data demonstrate: 1) our ability to synthesize the HydrAid Burn Dressing; 2) on-demand dissolution of the HydrAid Burn Dressing by application of a cysteine methyl ester solution; 3) lack of in vitro cytotoxicity or macrophage activation when exposed to the HydrAid Burn Dressing; 4) new data in response to reviewer comments demonstrates comparable healing to traditional bandages; 5) dissolution of the dressing in vivo on a 2nd degree burn; 6) efficacy in preventing bacterial infection in 2nd degree burn wounds treated with the HydrAid Burn Dressing; and, 7) easy ?spray-on? application for completely covering the intricate surfaces, digits, and webbing of a human hand. Two key Go/No-Go inflection points in the development of this technology are: 1) rigorous evaluation of whether the HydrAid Burn Dressing will prove beneficial (or at least non-harmful) to wound healing in a model relevant to human skin (e.g., pigs); and, 2) whether the synthesis can be scaled to produced material on a large, 200 g, scale while satisfying analytical testing protocols that would be appropriate for subsequent GMP manufacture. This proposal address these two key questions through the following aims: Aim 1: Determine the impact of the HydrAid Burn Dressing on wound healing in a second degree burn wound model in pigs. Aim 2: Scale-up production to the 200 g scale and develop analytics in-house at Ionic Pharma. Successful completion of these aims will enable a clear Go/No-Go decision (defined by prospective milestones) regarding the feasibility and value of further development of this technology.